Retroviral vectors are a common tool for gene delivery in that the ability of retroviral vectors to deliver a nucleic acid of interest into a broad range of cells makes them well suited for transferring genes to a cell. Retroviral vectors have been used in gene therapy as well as for therapeutic vaccines for infectious diseases and cancer. However, expression of multiple transgenes from a single retroviral vector genome (multicistronic expression) often results in unequal expression levels of the recombinant proteins due to, for example, competition of the different promoters for transcription factors or variability in function of internal ribosome entry site (IRES). In the case of delivery of nucleic acids to dendritic cells, interference phenomena on the level of expression, antigen processing or presentation, especially with certain tumor antigens, have been observed.
The present invention provides for improved retroviral vectors and methods of making same that facilitate expression of multiple transgenes.